rnh (formerly sdrA) mutants of Escherichia coli K-12 are devoid of RNase H activity. These mutants are capable of initiating repeated rounds of DNA replication in the absence of protein synthesis (stable DNA replication). The rnh mutants can despense with the normally required dnaA+ protein and to oriC site, the origin of DNA replication. In the absence of RNase H activity and the oriC site, at least four regions of the E. coli chromosome can be used as new origins (oriK) of DNA replication. Initiation of DNA replication of oriK requires the recA+ protein. In this application, genetic and biochemical experiments are propossed to elucidate the roles of RNase H and recombination functions (recA+) in the initiation of DNA replication. Also proposed are experiments to examine a possible involvement of stable DNA replication in the mutagenesis process that occurs as a result of cellular response to DNA damage. Efforts will also be made to isolate mutants in which initiation of DNA replication at oriC can occur in the absence of concomitant protein synthesis.